Anemia is common during human immunodeficiency virus (HIV) infection and is associated with increased HIV disease progression and higher mortality. Consequences of anemia include fatigue, a decreased sense of well-being, and a greater need for expensive recombinant human erythropoietin therapy, transfusions, and hospitalizations. Our studies show that the cumulative incidence of anemia is 100 percent among HIV-infected female injection drug users, and that iron deficiency anemia accounts for about half of the anemia. Iron deficiency is a major neglected problem of women, and no progress has been made in reducing the prevalence of iron deficiency among women in the U.S. over the last 30 years. Although iron supplementation can be used to prevent and treat iron deficiency anemia, concerns have been raised since iron supplementation and iron overload have been associated with increased HIV disease progression, higher mortality, and progression of hepatitis C (HCV) infection. These concerns have led to a dilemma about the use of iron supplements for iron deficiency and anemia in women with HIV and HCV. The prevalence of HCV is especially high among injection drug users in urban settings. Research is needed to determine whether the benefits of iron supplementation in this population outweigh the potential risks. Our specific aims are to determine whether a multivitamin and iron supplement can effectively reduce iron deficiency and anemia among HIV-positive and HIV-negative female injection drug users without worsening HIV or HCV infection. To address these aims, we propose to conduct a randomized controlled clinical trial of daily multivitamin and iron supplementation for 600 female injection drug users. Outcome measures include hemoglobin, indicators of HIV and HCV disease severity, and iron status, and the trial will be monitored by a data and safety monitoring committee. If the proposed trial shows that a multivitamin and iron supplement reduces anemia and does not worsen HIV or hepatitis C infection, the findings could be used to establish evidence-based guidelines for the prevention and/or reduction of anemia among women in the U.S. and elsewhere.